Factors determining phage stability/activity: challenges in practical phage application

ABSTRACT

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.

KEYWORDS:

• Phage activity
• stability
• storage conditions
• external factors

Article highlights

• Phages may lose their activity under different physico-chemical and physiological conditions;

• The production process of phage formulations, compounds and ingredients of the preparations, forms of preparation, storage conditions, and route of phage application may cause variations in phage titer;

• One should not generalize phages’ ability to retain activity under various conditions;

• Knowledge of factors which may influence individual phage properties may help effective phage application as therapeutics;

The described factors should be studied in detail to help improve phage therapy research and especially planning as well as executing successful clinical trials that could lead to market authorization of phage products.

Declaration of interest

R Międzybrodzki, B Weber-Dąbrowska and A Górski are co-inventors of patents owned by the L. Hirszfeld Institute and covering phage preparations. The other authors declare that the research was conducted in the absence of any commercial of financial relationships that could be construed as a potential conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by statutory funds from the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science.